Multiple Routes to Oncogenesis are Promoted by the Human Papillomavirus-Host Protein Network
A partir d'une cartographie du réseau d'interactions entre protéines du papillomavirus humain (HPV) et protéines de l'hôte, cette étude identifie un ensemble de mécanismes cellulaires par lesquels un virus tel que le HPV induit une oncogenèse
We have mapped a global network of virus-host protein interactions by purification of the complete set of Human Papillomavirus (HPV) proteins in multiple cell lines followed by mass spectrometry analysis. Integration of this map with tumor genome atlases shows that the virus targets human proteins frequently mutated in HPV(-) but not HPV(+) cancers, providing a unique opportunity to identify novel oncogenic events phenocopied by HPV infection. For example, we find that the Nrf2 transcriptional pathway, which protects against oxidative stress, is activated by interaction of the Nrf2 regulator Keap1 with the viral protein E1. We also demonstrate that the L2 HPV protein physically interacts with the RNF20/40 histone ubiquitination complex and promotes tumor cell invasion in an RNF20/40-dependent manner. This combined proteomic and genetic approach provides a systematic means to study the cellular mechanisms hijacked by virally induced cancers.
Cancer Discovery 2018